• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Research for the development of methods to control age-related diseases and bone diseases

Research Project

Project/Area Number 20K20496
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Studies on the Super-Aging Society
Research InstitutionJuntendo University (2021-2022)
The University of Tokyo (2020)

Principal Investigator

Negishi Takako  順天堂大学, 大学院医学研究科, 特任准教授 (90451905)

Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2020: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Keywords骨代謝学 / 加齢性疾患 / 骨粗鬆症 / 破骨細胞 / 骨芽細胞 / 骨代謝 / 加齢 / 老化 / 認知疾患
Outline of Research at the Start

本研究は下記の2つの大目的を達成するための研究を計画する。
(I)認知能、記憶・学習を司る脳・神経系が骨代謝を制御するか否か?【脳・神経→骨】
(II)力学的負荷/リハビリテーションは記憶・学習能力を改善するか?【骨→脳・神経】
また(III)骨と脳・神経のリンクを司る分子実態の同定を目指す。

Outline of Final Research Achievements

Using a mouse model of Alzheimer’s disease, we found that amyloid-b deposited in bone tissue and caused bone loss, suggesting that deposition of amyloid-b in bone tissue may occur independently of its deposition in the brain and of impaired cognitive function and learning. In this mouse model, mild exercise by treadmill induced tibia fracture susceptibility resulted from gene expression changes in certain circulating cells and knee joint cells around the time of onset of behavioral abnormalities. It was suggested that a degeneration-dependent humoral factor in the brain causes bone fragility. This bone fragility was not detected in mice with spontaneous memory deficits, suggesting neuropathic amyloid-b-dependent bone fragility.

Academic Significance and Societal Importance of the Research Achievements

加齢とともに心身の活力(運動機能や認知機能等)が低下するフレイルやロコモーティブシンドローム(ロコモ)は要介護状態の前段階であり、フレイルや初期のロコモの段階で積極的に改善をめざすことができれば超高齢社会で要介護人口の増加に歯止めをかける一助となる。その意味で、リハビリや運動療法は初期の認知症やフレイルを発症した高齢者に推奨される。リハビリや運動療法が認知症にも効果があることを分子レベルで証明できれば、それを人為的な治療・薬剤開発の基盤にできる。運動器と脳・神経系の関連を担う因子を探求することは、学術的にも新たな発見につながり、社会的にも新規制御法の開発に繋がる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Anterior meniscus extrusion is associated with anterior tibial osteophyte width in knee osteoarthritis-The Bunkyo Health Study2023

    • Author(s)
      Adili A, Kaneko H, Aoki T, Liu L, Negishi Y, Tomura J, Wakana S, Momoeda M, Arita H, Hada S, Shiozawa J, Kubota M, Someya Y, Tamura Y, Aoki S, Watada H, Kawamori R, Negishi-Koga T, Okada Y, Ishijima M
    • Journal Title

      Osteoarthritis and Cartilage Open

      Volume: 5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periosteal stem cells control growth plate stem cells during postnatal skeletal growth2022

    • Author(s)
      Tsukasaki M, Komatsu N, Negishi-Koga T, Huynh NC, Muro R, Ando Y, Seki Y, Terashima A, Pluemsakunthai W, Nitta T, Nakamura T, Nakashima T, Ohba S, Akiyama H, Okamoto K, Baron R, Takayanagi H
    • Journal Title

      Nat Commun

      Volume: 13 Issue: 1 Pages: 4166-4166

    • DOI

      10.1038/s41467-022-31592-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis.2021

    • Author(s)
      Hosonuma M, Sakai N, Furuya H, Kurotaki Y, Sato Y, Handa K, Dodo Y, Ishikawa K, Tsubokura Y, Negishi-Koga T, Tsuji M, Kasama T, Kiuchi Y, Takami M, Isozaki T.
    • Journal Title

      Rheumatology

      Volume: 60 Pages: 408-419

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 抗RANKLモノクローナル抗体がマウス脊椎固定術モデルの骨癒合に及ぼす影響2021

    • Author(s)
      谷 聡二, 石川 紘司, 古賀 貴子, 工藤 理史, 松岡 彰, 丸山 博史, 山村 亮, 早川 周良, 関水 壮哉, 土谷 弘樹, 辻 まゆみ, 木内 祐二, 永井 隆士, 豊根 知明, 稲垣 克記
    • Journal Title

      Journal of Spine Research

      Volume: 12 Pages: 538-538

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myelination during fracture healing in vivo in myelin protein zero (p0) transgenic medaka line2020

    • Author(s)
      Dodo Y, Chatani M, Azetsu Y, Hosonuma M, Karakawa A, Sakai N, Negishi-Koga T, Tsuji M, Inagaki K, Kiuchi Y, Takami M
    • Journal Title

      Bone

      Volume: 133 Pages: 115225-115225

    • DOI

      10.1016/j.bone.2020.115225

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of lipid metabolism on mouse incisor dentinogenesis.2020

    • Author(s)
      Kurotaki, Y., Sakai, N., Miyazaki, T., Hosonuma, M., Sato, Y., Karakawa, A., Chatani, M., Myers, M., Suzawa, T., Negishi-Koga, T., Kamijo, R., Miyazaki, A., Maruoka, Y., Takami, M.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 5102-5102

    • DOI

      10.1038/s41598-020-61978-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice2020

    • Author(s)
      Kiyohara S, Sakai N, Handa K, Yamakawa T, Ishikawa K, Chatani M, Karakawa A, Azetsu Y, Munakata M, Ozeki M, Negishi-Koga T, Takami M
    • Journal Title

      J Oral Biosci

      Volume: - Issue: 2 Pages: 131-138

    • DOI

      10.1016/j.job.2020.03.003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel gene Merlot inhibits differentiation and promotes apoptosis of osteoclasts2020

    • Author(s)
      Yamakawa Tomoyuki、Okamatsu Nobuaki、Ishikawa Koji、Kiyohara Shuichi、Handa Kazuaki、Hayashi Erika、Sakai Nobuhiro、Karakawa Akiko、Chatani Masahiro、Tsuji Mayumi、Inagaki Katsunori、Kiuchi Yuji、Negishi-Koga Takako、Takami Masamichi
    • Journal Title

      Bone

      Volume: 138 Pages: 115494-115494

    • DOI

      10.1016/j.bone.2020.115494

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Mouse model of uncoupled bone remodeling upon discontinuation of anti-RANKL antibody therapy2023

    • Author(s)
      Koji Ishikawa, Soji Tani, Nobuhiro Sakai, Yoshifumi Kudo, Hideyo Horiuchi, Hiromi Kimura-Suda, Masamichi Takami, Mayumi Tsuji, Katsunori Inagaki, Yuji Kiuchi, Takako Negishi-Koga
    • Organizer
      The American Society for Bone and Mineral Research
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インターロイキン-6による変形性膝関節症由来骨棘細胞のスフェロイド形成抑制作用2023

    • Author(s)
      根岸義文、 Adili Arepati、 Susana de Vega、百枝雅裕、金子晴香、Mehmet Zeynel Cilek、良永知穂、高藤和輝、大塚祐多、下田将之、根岸貴子、石島旨章、岡田保典
    • Organizer
      第55回日本結合組織学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗RANKL抗体治療の中断による骨代謝破綻の機序2021

    • Author(s)
      石川 紘司, 谷 聡二, 坂井 信裕, 高見 正道, 堀内 秀与, 木村 廣美[須田], 辻 まゆみ, 木内 祐二, 稲垣 克記, 根岸 貴子[古賀]
    • Organizer
      日本骨形態計測学会
    • Related Report
      2021 Research-status Report
  • [Presentation] パーキンソン病モデルマウスを用いたドパミン神経と骨代謝についての解析2020

    • Author(s)
      飯田和章
    • Organizer
      日本骨形態計測学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 破骨細胞に高発現する未同定遺伝子の解析2020

    • Author(s)
      山川 智之
    • Organizer
      昭和学士会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウスを用いたパーキンソン病における骨代謝制御の解析2020

    • Author(s)
      飯田 和章
    • Organizer
      昭和学士会
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi